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  • Writer's pictureP.K. Peterson

Fever Is Your Friend

- Parmenides, pre-Socratic Greek philosopher

“Fever itself is Nature’s instrument.”

- Thomas Sydenham, 17th century physician (“the English Hippocrates”)

We are entering our fourth year of fighting the COVID-19 pandemic and at the same time are battling two other viruses: the influenza virus and the respiratory syncytial virus. This so-called viral “tripledemic” is hitting the U.S. with full force. Many Germ Gems readers may have recently experienced a fever—a common symptom of a viral infection. In this week’s Germ Gems post, I provide a definition for the term “fever” and review why nature provided us with this incredibly elegant mechanism for fighting infections.

What exactly is a fever? Fever is defined as an elevation of body temperature above normal that is driven by a resetting of the temperature regulating center in the brain (an area that functions much like a thermostat). But what is a “normal” body temperature and what is meant by a resetting of the temperature regulating center in the brain?

For decades 98.6F (38C) was considered the normal body temperature for adults; that is no longer so. Due to recent research by infectious diseases experts at Stanford University, a temperature of 97.5F (36.6C) is now considered normal. (In my February 14, 2020 Germ Gems post “As the Climate Warms Homo sapiens Cool: How’s that for Irony?” I dealt with the question of what is the “normal” body temperature for adults.)

The physiological processes underlying the generation of a fever are exquisite and complex. Current evidence indicates that cytokines produced by activated immune cells target the brain’s thermostat leading to an increased body temperature due to a series of behaviors, such as, going to bed and piling on blankets, and mechanisms, like “chills” (shaking of muscles to generate heat).

The “resetting of temperature regulating center of the brain” aspect of fever needs to be stressed because body temperature can be raised to life-threatening levels without any change in the brain’s thermostat. This situation is called hyperthermia—not fever. Heat stroke is a life-threatening form of hyperthermia. When heat stroke occurs, the body temperature can rise to 106°F (41.1C) or higher, that is, temperatures that denature proteins and cause cellular damage.(Fueled by global warming, at least 15,000 people died of heat stroke this past year.) The treatment for hyperthermia is the urgent lowering of body temperature.

Why do our bodies mount a fever when infected? In contrast to hyperthermia, fever per se doesn’t damage or kill the host. Instead, fever is a host defense mechanism and interfering with a fever’s development can be deleterious.

In the journal Science in 1975, several physiologists at the University of Michigan published the landmark study “Fever and survival.” These researchers designed a very clever experiment to test whether fever was beneficial or harmful involving the cold-blooded animal Dipsosaurus dorsalis, aka the iguana. To raise their body temperature cold-blooded animals must find a warm environment (you may have seen iguanas basking in the sun). The researchers designed containers that allowed or prevented access of the animals to an area with a temperature set in the febrile range (40C).

When iguanas were challenged with the gram-negative bacterium, Aeromonas hydrophila, and were allowed access to the heated compartment all the animals survived. On the other hand, iguanas that were kept at room temperature after a bacterial challenge, all died. And when animals permitted access to the warm environment were given an antipyretic drug, they also all died. From these experiments, the researchers concluded, “An elevation in temperature following experimental bacterial infection results in a significant increase in host survival.”

At about the same time of the Michigan study, other reports appeared showing that patients with bloodstream infection (bacteremia) who did not mount a fever had a much higher mortality rate than those who developed a fever. To help explain the beneficial effects of fever on survival of infections, a number of subsequent studies demonstrated that certain pathogens “can’t stand the heat,” that is, they were killed by temperatures in the febrile range. Other research also showed that various functions of immune cells (lymphocytes, macrophages, and neutrophils) were enhanced when they were exposed to elevated temperatures.

What not to do. The first thing not to do when a febrile illness strikes is to take an antipyretic. Remember fever is your friend. Surprisingly, to this day that message isn’t widely appreciated. (I’ve often wondered if there’s a conspiracy on the part of the antipyretic industry, i.e., the makers of aspirin, acetaminophen, and ibuprofen.)

In addition, you need to curb a second reflex, that is, to request an antibiotic to treat fever. This is because antibiotics only work against bacterial infections, which are by far outnumbered by viral infections as a cause of fever.

What should you do when you develop a fever? The first thing you should do when you develop a fever is to determine its cause. Fever (temperatures over 97.5F) is considered one of the four vital signs, and if any of the other signs: hypotension (systolic blood pressure less than 100), tachycardia (pulse over 100/minute), or tachypnea (respiratory rate over 20/minute) accompanies your fever, contact your primary care provider who can make a diagnosis and follow it with the appropriate treatment.

Most fevers this time of the year, however, are caused by viral infections, and those responsible for the “tripledemic” are high on the list of potential culprits. If you have symptoms of an upper respiratory tract infection, SARS-CoV-2, the cause of COVID-19, can be ruled out or in with a rapid, in-home antigen test. If the test is negative, the only other viral infection for which there is treatment, that is, influenza, should be considered, and if you are very ill, it’s time to contact your primary care provider for advice about next steps.

The causes of fever are vast, and although a myriad of infections head the list of potential etiologies, other diagnoses, e.g., cancer, autoimmune disorders, and drug fever, are to be considered depending on your medical history. Fortunately, most of the time fever is caused by a viral infection that “burns itself out.” But if you have any concerns, you shouldn’t hesitate to contact your primary care provider. When you have a perplexing pyrexia (unexplained fever), they’re your most trustworthy ally.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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